Deciphering lung granulomas in HIV & TB co-infection: unveiling macrophages aggregation with IL6R/STAT3 activation

Li, Qian1,2; Wang, Cheng1,2; Gou, Jizhou3; Kitanovski, Simo4; Tang, Xiangyi1,2; Cai, Yixuan5; Zhang, Chenxia5; Zhang, Xiling1,2; Zhang, Zhenfeng6; Qiu, Yuanwang5; Zhao, Fang1,2; Lu, Mengji7; He, Yun1,2; Wang, Jun1,2,4,5; Lu, Hongzhou1,2

2024-12-31

10.1080/22221751.2024.2366359

EMERGING MICROBES & INFECTIONS   影响因子和分区

2222-1751

Tuberculosis (TB) remains a leading cause of mortality among individuals coinfected with HIV, characterized by progressive pulmonary inflammation. Despite TB's hallmark being focal granulomatous lung lesions, our understanding of the histopathological features and regulation of inflammation in HIV & TB coinfection remains incomplete. In this study, we aimed to elucidate these histopathological features through an immunohistochemistry analysis of HIV & TB co-infected and TB patients, revealing marked differences. Notably, HIV & TB granulomas exhibited aggregation of CD68 + macrophage (M phi), while TB lesions predominantly featured aggregation of CD20+ B cells, highlighting distinct immune responses in coinfection. Spatial transcriptome profiling further elucidated CD68+ M phi aggregation in HIV & TB, accompanied by activation of IL6 pathway, potentially exacerbating inflammation. Through multiplex immunostaining, we validated two granuloma types in HIV & TB versus three in TB, distinguished by cell architecture. Remarkably, in the two types of HIV & TB granulomas, CD68 + M phi highly co-expressed IL6R/pSTAT3, contrasting TB granulomas' high IFNGRA/SOCS3 expression, indicating different signaling pathways at play. Thus, activation of IL6 pathway may intensify inflammation in HIV & TB-lungs, while SOCS3-enriched immune microenvironment suppresses IL6-induced over-inflammation in TB. These findings provide crucial insights into HIV & TB granuloma formation, shedding light on potential therapeutic targets, particularly for granulomatous pulmonary under HIV & TB co-infection. Our study emphasizes the importance of a comprehensive understanding of the immunopathogenesis of HIV & TB coinfection and suggests potential avenues for targeting IL6 signaling with SOCS3 activators or anti-IL6R agents to mitigate lung inflammation in HIV & TB coinfected individuals.

Macrophage human immunodeficiency virus Mycobacterium tuberculosis multiplex staining spatial transcriptomics IL-6R/STAT3 pathway SOCS3

SCI

英语

通讯

Immunology ; Infectious Diseases ; Microbiology

Immunology ; Infectious Diseases ; Microbiology

WOS:001249759900001

TAYLOR & FRANCIS LTD

Web of Science

1.Third Peoples Hosp Shenzhen, Natl Clin Res Ctr Infect Dis, Shenzhen 518112, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Affiliated Hosp 2, Shenzhen 518112, Guangdong, Peoples R China
3.Shenzhen Third Peoples Hosp, Natl Clin Res Ctr Infect Dis, Dept Pathol, Shenzhen, Peoples R China
4.Univ Duisburg Essen, Bioinformat & Computat Biophys, Essen, Germany
5.Jiangnan Univ, Peoples Hosp Wuxi 5, Clin Res Ctr, Wuxi, Peoples R China
6.Southern Univ Sci & Technol, Sch Publ Hlth & Emergency Management, Affiliated Hosp 2, Shenzhen, Peoples R China
7.Univ Duisburg Essen, Essen Univ Hosp, Inst Virol, Essen, Germany

Li, Qian,Wang, Cheng,Gou, Jizhou,et al. Deciphering lung granulomas in HIV & TB co-infection: unveiling macrophages aggregation with IL6R/STAT3 activation[J]. EMERGING MICROBES & INFECTIONS,2024,13(1).

Li, Qian.,Wang, Cheng.,Gou, Jizhou.,Kitanovski, Simo.,Tang, Xiangyi.,...&Lu, Hongzhou.(2024).Deciphering lung granulomas in HIV & TB co-infection: unveiling macrophages aggregation with IL6R/STAT3 activation.EMERGING MICROBES & INFECTIONS,13(1).

Li, Qian,et al."Deciphering lung granulomas in HIV & TB co-infection: unveiling macrophages aggregation with IL6R/STAT3 activation".EMERGING MICROBES & INFECTIONS 13.1(2024).